Analysis of treatment guidelines for Alzheimer's disease

Nefiracetam powder can enhance cognitive ability and prevent the damage of learning and memory through its effect on the cerebral cortex. It does not have the characteristics of muscarinic receptor agonists and antagonists, nor inhibit the activity of acetylcholinesterase. Therefore, its anti forgetting and memory-enhancing effect occur by improving the release of acetylcholine in the cerebral cortex. The normal function of the cholinergic nerve depends on the innervation of the glutamatergic nerve, which may depend on the protein kinase of camp to enhance the activity of the Ca2 plus channel and enhance the release of acetylcholine. Clinical trial data suggest that raw material Nefiracetam may have the potential to improve recognition function and neuroprotection. At the same time, it also shows an antiepileptic effect.

There is supplementary knowledge about Alzheimer's disease.

In the past two or three decades, the research on Alzheimer's disease (AD) has become more and more in-depth. People continue to improve their understanding of it. The progress of many auxiliary examinations, especially cerebrospinal fluid markers and imaging examination methods, has effectively improved the accuracy of AD diagnosis. In terms of treatment, people also pay more attention to various combined symptoms of AD and strive to improve the quality of life of patients.

On the basis of many studies, many diagnosis and treatment guidelines related to AD have been published at home and abroad, especially the guidelines for the diagnosis and treatment of ad issued by the European Neurology Association in 2010 and the guidelines for the diagnosis and treatment of dementia issued by the Chinese Medical Association in 2010, And the diagnostic criteria for AD (nia-aa criteria) issued by the National Institute on Aging (NIA) and the Alzheimer's Association (AA) in 2011. Based on the above guidelines / diagnostic criteria, we briefly introduce the standardized diagnosis and treatment of AD.

1. AD diagnosis process

1.1 make clear the diagnosis of dementia. For patients with severe cognitive impairment, we should first establish the diagnosis of dementia. Dementia is a kind of syndrome. When patients have cognitive or mental symptoms and meet the following characteristics, the diagnosis of dementia can be considered.

(1) Patients' symptoms affect their daily work and life.

(2) The cognitive level and function decreased compared with that before onset.

(3) Delirium and other mental diseases (such as depression) were excluded.

(4) Based on medical history and objective cognitive examination, the patient was judged to have cognitive impairment.

(5) The following cognitive domains and mental symptoms have at least two impairments: ① the ability to learn and remember new information; ② Executive function; ③ Visuospatial ability; ④ Language function; ⑤ There are mental symptoms such as personality and abnormal behavior.

1.2 after establishing the diagnosis of AD and clarifying the diagnosis of dementia, it is necessary to further determine the etiology of dementia according to medical history, physical examination, neurological examination, neuropsychological assessment, laboratory, and imaging examination, and pay special attention to excluding some treatable diseases.

The current medical history should pay attention to which cognitive domains are damaged, the evolution of the disease, the impact on daily work and life, and related noncognitive impairment. Because dementia patients have cognitive impairment and lack of self-knowledge, the medical history should be confirmed or supplemented by insiders as much as possible.

Physical examination is of great value for the etiological diagnosis of dementia. General and neurological physical examination should be carried out in detail, which is helpful to distinguish an ad from vascular dementia, Lewy body dementia, progressive supranuclear palsy, and other diseases causing dementia.

Neuropsychological assessment can objectively assess whether patients have a cognitive impairment, the characteristics and severity of cognitive impairment, and the accompanying psychobehavioral symptoms. It is an important means to diagnose dementia.

Laboratory examination (such as blood and cerebrospinal fluid) and imaging examination can help to clarify the cause of dementia. Cerebrospinal fluid test (a) 42. Tau protein, phosphorylated tau protein), structural brain magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission computed tomography (FDG-PET), PETA Imaging, single-photon emission computed tomography (SPECT), and other laboratory and imaging examinations have improved the accuracy of AD diagnosis.

Nia-aa standard divides the diagnosis of ad dementia into probable AD dementia, probable AD dementia, and probable or probable AD dementia with AD pathophysiological markers. The first two are applicable to almost all medical institutions, and the third is applicable to medical centers that have carried out ad-related biomarker examinations. At present, it is mainly used for scientific research. In addition, ad dementia confirmed by pathophysiology was also mentioned.

1.2.1 probable AD dementia can be diagnosed as probable AD dementia if it meets the following core clinical criteria: (1) it meets the above diagnostic criteria of dementia; (2) The onset of the disease is insidious, and the symptoms gradually appear within a few months to years; (3) The patient's subjective report or informed person's observation to obtain a clear history of cognitive impairment; (4) In medical history and physical examination, the impairment of the initial and most prominent cognitive domain is often memory impairment, in addition, there should be a cognitive domain impairment; (5) When there is evidence of cerebrovascular disease, Lewy body dementia, frontotemporal dementia, and other diseases, ad dementia should not be diagnosed.

1.2.2 possible ad dementia has one of the following conditions, that is, it is diagnosed as possible ad dementia: (1) the course of the disease is not typical and meets Articles 1 and 4 of the above core clinical standards, but cognitive impairment can occur suddenly, or the medical history is not detailed enough, or the evidence of objective cognitive decline is insufficient; (2) The etiology is uncertain and meets (1) (4) of the above-mentioned core clinical criteria of AD, but there is evidence of cerebrovascular disease, Lewy body dementia, and other diseases.

1.2.3 possible or possible ad dementia with AD pathophysiological markers has introduced cerebrospinal fluid and imaging markers on the basis of the above clinical diagnosis.

The nia-aa standard divides these biomarkers into two categories. (1) Brain a Marker of deposition: cerebrospinal fluid a 42 reduction and pet a Imaging. (2) Biomarkers of neuronal injury: increased tau protein in cerebrospinal fluid, decreased glucose metabolism in the temporal-parietal cortex by FDG-PET, atrophy of basal, medial, or lateral temporal lobe, and atrophy of medial parietal cortex by structural MRI.

1.2.4 ad dementia confirmed by pathophysiology can be diagnosed as ad dementia confirmed by pathophysiology if the patient meets the above clinical and cognitive criteria of ad dementia and proves the existence of AD pathology by neuropathological examination.

Treatment of abnormal symptoms of mental behavior in Ad

The EFNS and APA guidelines for non-drug treatment of abnormal symptoms of mental behavior (BPSD) suggest looking for incentives for BPSD in AD patients, such as whether they have discomfort in life, environment, and body, correcting their potential causes, and taking nondrug management (Level C).

Selective serotonin (5-HT) reuptake inhibitors (SSRIs) instead of tricyclic antidepressants can supplement the decrease of 5-HT caused by AD pathology and improve depression-related neuropsychiatric symptoms, such as aggression, anxiety, apathy, and mental disorders, Traditional tricyclic antidepressants (such as amitriptyline and imipramine) have anticholinergic adverse reactions and should be avoided.

Antipsychotics can control BPSD in AD patients, but their adverse reactions are large and should be used in a small amount of short-term when they have to be used. The adverse reactions of atypical antipsychotics such as aripiprazole, quetiapine, olanzapine, and risperidone include: increasing the risk of death Cardiovascular and cerebrovascular accidents, delayed motion disorders, weight gain, diabetes, excessive sedation, confusion, and cognitive function deterioration. Therefore, caution should be exercised in the use of such drugs, the lowest effective dose should be given, and the potential benefits and risks of antipsychotic drugs to patients and their families should be informed, especially the risk of death. There is no evidence that traditional antipsychotics are safer than atypical antipsychotics in the risk of stroke or death, traditional drugs lack definite evidence and have greater adverse reactions (Level B).

Benzodiazepines may have a certain effect on the anxiety symptoms of AD patients. APA guidelines believe that benzodiazepines have more adverse reactions and fewer benefits than antipsychotics. They are only occasionally used in patients with some irritation or anxiety, and long-term use should be avoided. The adverse reactions of benzodiazepines include excessive sedation, increased falls, respiratory depression Deterioration of cognitive function, delirium, and increased risk of depression. Lorazepam and oxazepam have no active metabolites, and their effects are better than those of drugs with a longer half-life (diazepam or clonazepam), while short-acting drugs are more prone to falls and hip fractures. Benzodiazepine dependence is also a risk worthy of attention.

APA guidelines for the application of emotional stabilizers point out that the use of low-dose carbamazepine has moderate benefits for patients with AD provocative symptoms. Carbamazepine is not recommended as a conventional drug for patients with dementia. When antipsychotics are ineffective, carbamazepine and valproate can be considered. EFNS guidelines suggest that carbamazepine may be helpful for aggressive behavior, but most valproic acid tests are negative. In clinical practice, the author found that some AD patients have temporal lobe epilepsy, which is clinically manifested as mental and behavioral symptoms. Temporal lobe epilepsy is easy be misdiagnosed as the mental symptoms of AD. carbamazepine may control the mental and behavioral abnormalities due to anti temporal lobe epilepsy in some patients, while it can effectively control the mental and behavioral symptoms of ad caused by nontemporal lobe epilepsy in others.

The guidelines for the treatment of sleep disorders believe that there are little data on the efficacy of nonbenzodiazepines such as trazodone, zolpidem, or zaleplon in the treatment of sleep disorders in AD patients, which can be treated individually in combination with the clinical effect of patients. Benzodiazepines are not recommended for use or only for short-term use because of their adverse reactions. Diphenhydramine is not recommended because of its anticholinergic effect. Antipsychotics should not be used only to treat sleep disorders.

Other aids for Alzheimer's disease

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin are not used in the treatment of AD (level a) but can be used in AD patients with other indications (such as the prevention of cardiovascular events). There were obvious immune-inflammatory reactions around senile plaques in AD patients, such as T lymphocyte infiltration, the presence of cytokines, complement, and immune response-related proteins, but this phenomenon was not found in the age-matched healthy control group. APA guidelines point out that the clinical study of NSAIDs alone, such as aspirin, has not shown that it has a basis for the treatment of AD, but aspirin is recommended when controlling the risk factors of AD, such as hypertension, hyperlipidemia, and stroke.

Antioxidants alone have no effective basis for the treatment of AD, and the oxidative stress response is increased Amyloid (a) ) Neurotoxic effects, antioxidants can protect neurons from a Induced neurotoxicity. For example, Ginkgo biloba preparation, vitamin E and selegiline, the guidelines point out that there is no basis to show that the use of antioxidants alone can benefit patients with AD. at present, the meta-analysis of the safety of vitamin E clinical trial found that it has the risk of dose-dependent mortality. It is suggested that vitamin E should not be used in the treatment of AD (level a).

The efficacy and safety of intelligence promoting drugs in the treatment of AD are uncertain (level a). Intelligence promoting drugs include brain metabolic activators (mesylate ergot mixture, such as dihydro ergot, nicergoline, etc.) and pyrrolidone derivatives (piracetam, aniracetam, Nefiracetam, coluracetam). Ergot alkaloids can enhance the metabolism of brain cells, increase the role of oxygen uptake and glucose by brain cells, nourish nerve cells and promote the transmission of neurotransmitters, so as to improve cognitive function. Pyrrolidone derivatives can increase brain metabolic function, and their main mechanism is to act on presynaptic membrane ion channels in neurotransmission. By enhancing the current of potential-dependent calcium channels of nerve cells, the intake of calcium ions is enhanced, so as to promote the release of neurotransmitters. The guidelines do not recommend the routine use of these drugs, but they also point out that clinicians often use them in selective patients or adjuvant treatment because their efficacy and safety are uncertain.

The adjuvant treatment of drugs to improve cerebral blood circulation in AD patients has obvious cerebral vascular amyloidosis (CAA) and cerebral atherosclerosis, which can lead to cerebral vascular stenosis and cerebral ischemia. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) have verified the phenomenon of reduced cerebral blood flow perfusion in AD patients, although none of the guidelines involves the field of traditional Chinese medicine, However, at present, China's traditional Chinese medicine community is carrying out a lot of research on the treatment of ad with traditional Chinese medicine to improve cerebral blood circulation, which can reduce the damage of nerve cell function caused by secondary cerebral ischemia. The exact results need to be clinically verified.

Patients with mild to moderate AD can use cognitive stimulation or rehabilitation therapy (good practice reference). Professional cognitive rehabilitation therapy can improve patients' function and reduce the need for care (Level B). The guidelines suggest that it should be supplemented by rehabilitation therapy, including (1) stimulation-oriented therapy, such as recreational activities, art therapy, music therapy, and pet therapy. (2) Emotion-oriented therapy, that is, supportive psychotherapy helps alleviate the early loss of function of patients. (3) Recall therapy has research support for improving emotional and behavioral symptoms. (4) Cognitive-oriented therapy, such as ontology positioning, cognitive retraining, and skill training for special cognitive defects, can not benefit patients for a long time.

Clinical application of Nefiracetam

Nefiracetam medicine is used to treat cerebrovascular diseases. It can enhance cognitive ability and prevent the damage of learning and memory through its effect on the cerebral cortex. It does not have the characteristics of muscarinic receptor agonists and antagonists, nor inhibit the activity of the acetylcholine enzyme. Therefore, its anti forgetting and memory-enhancing effect occur by improving the release of acetylcholine in the cerebral corts